Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of nonsmall cell lung cancer(NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy(IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Biological effects of human lung cells MRC-5 in CBCT positioning for image-guided radiotherapy

Image-guided radiotherapy(IGRT) provides precise positioning for the tumor target, but it may bring extra irradiation dose in the target positioning with a cone beam CT(CBCT) which has been increasingly used in IGRT. In this work, we focused on biological effects of the low-dose irradiation in IGRT, which have not been considered so far. Primary human fibroblasts cells from the lung and MRC-5 were irradiated by a CBCT. DNA doublestrand breaks(c-H2 AX foci) and micronucleus frequency of the irradiated samples were analyzed. Compared to the control, the c-H2 AX foci yields of the samples irradiated to 16 m Gy increased significantly, and the micronuclei rate of the samples irradiated for 3 days increased notably. The dose by imaging guidance device can be genotoxic to normal tissue cells, suggesting a potential risk of a secondary cancer. The effects, if confirmed by clinical studies,should be considered prudentially in designing IGRT treatment plans for the radiosensitive population, especially for children.

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers

BACKGROUND Image-guided radiotherapy(IGRT)has significantly improved the precision in which radiotherapy is delivered in cancer treatment.Typically,IGRT uses bony landmarks and key anatomical structures to locate the tumor.Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue.The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied.However,placement requires expertise and specialized endoscopic ultrasound equipment.This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT.AIM To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients.METHODS A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne,Australia was conducted.Up to four liquid fiducials were inserted per patient,each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil(Lipiodol;Aspen Pharmacare)and n-butyl 2-cyanoacrylate(Histoacryl®;B.Braun).A 23-gauge injector(Cook Medical)was used for the injection.All procedures were performed by or under the supervision of a gastroenterologist.Liquid fiducial-based IGRT(LF-IGRT)consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy.Patients received standard-IGRT(S-IGRT)if fiducial visibility was insufficient,consisting of bone match as a surrogate for tumor position.Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments.RESULTS 52 patients were referred for liquid fiducial placement within the study period.A total of 51 patients underwent liquid fiducial implantation.Of these a total of 31 patients received radiotherapy.Among these,the median age was 77.4 years with a range between 57.5 and 88.8,and 64.5%were male.Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT.There were no complications after endoscopic implantation of liquid fiducials in our cohort.The cohort overall survival(OS)post-radiotherapy was 19 mo(range 0 to 87 mo).Whilst the progression-free survival(PFS)post-radiotherapy was 13 mo(range 0 to 74 mo).For those treated with curative intent,the median OS was 22.0 mo(range 0 to 87 mo)with a PFS median of 14.0 mo(range 0 to 74 mo).Grade 3 complication rate post-radiotherapy was 29%.CONCLUSION LF-IGRT is feasible in 87.1%of patients undergoing liquid fiducial placement through standard gastroscopy injection technique.Our cohort has an overall survival of 19 mo and PFS of 13 mo.Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

Technical advances in external radiotherapy for hepatocellular carcinoma

Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma(HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy(IMRT), stereotactic ablative body radiotherapy(SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Modified simultaneous integrated boost radiotherapy for an unresectable huge refractory pelvic tumor diagnosed as a rectal adenocarcinoma

A clinical trial of radiotherapy with modified simultaneous integrated boost(SIB)technique against huge tumors was conducted.A 58-year-old male patient who had a huge pelvic tumor diagnosed as a rectal adenocarcinoma due to familial adenomatous polyposis was enrolled in this trial.The total dose of 77 Gy(equivalent dose in 2Gy/fraction)and 64.5 Gy was delivered to the center of the tumor and the surrounding area respectively,andapproximately 20%dose escalation was achieved with the modified SIB technique.The tumor with an initial maximum size of 15 cm disappeared 120 d after the start of the radiotherapy.Performance status of the patient improved from 4 to 0.Radiotherapy with modified SIB may be effective for patients with a huge tumor in terms of tumor shrinkage/disappearance,improvement of QOL,and prolongation of survival.

Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy

In single photon emission computed tomography-based three-dimensional radiotherapy(SPECT-B-3DCRT), im-ages of Tc-99 m galactosyl human serum albumin(GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation im-ages. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepato-cellular carcinoma(HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none ex-perienced fatal radiation-induced liver disease(RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients givendoses of ≥ 20 Gy(FLV20Gy). Therefore, FLV20 Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20 Gy as a qualitative index, we propose a quantitative indicator, F 20 Gy, which was calculated as F 20 Gy = 100% ×(the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).

Stereotactic Radiotherapy Planning Using Modified Dynamic Conformal Arcs under Considering the Possibility for Amended Visual Organ Displacement Resulting from Early Tumor Shrinkage during Treatment for Perioptic Involvement of Myeloma

Treatment planning of radiotherapy for skull base involvement of multiple myeloma presenting with visual impairment should be optimized to alleviate symptoms immediately and sufficiently while minimizing toxicities. Two such patients were treated with fractionated stereotactic radiotherapy by using Dynamic Conformal Arcs (DCA) under image guidance based on bony anatomy alignment. DCA planning was optimized after considering the possibility for amendment of visual organ displacement resulting from early tumor shrinkage during treatment through 1) the use of a target volume with modified geometry as a surrogate for leaf adaptation in order to improve target coverage, and 2) manual adjustment of a subset of leaf positions to reduce the dose gradient immediately inside the target boundary facing the visual organs and to eliminate an undesirable dose hotspot. In both cases, anticipated geometric changes in the target volume associated with improvement of visual organ displacement toward the target centroid were observed before the completion of treatment. Favorable visual functional outcomes as well as local tumor control were achieved during 14 months and 4 months follow-up periods. Notably, inexorable visual loss in one patient was fully reversed within one month after radiotherapy. We described the modification techniques for DCA planning in detail.

Radiotherapy reliability analysis based on PSA method

The reliability of radiotherapy was evaluated and effective approaches were obtained in order to improve radiotherapy quality by using the Probabilistic Safety Assessment(PSA) method. This study investigated the feasibility of the PSA method being applied to radiotherapy through Image-guided Radiotherapy(IGRT) and chest tumor irradiation. A fault tree has been constructed after analyzing causal relationship of the events.After calculating Risk A, a total inaccuracy radiotherapy probability and the importance of all base events were obtained. The probability of inaccurate radiotherapy was 2.87%. Under the condition that the target delineation was perfectly right, the accuracy of radiotherapy significantly improved. With the calculation without Conebeam Computed Tomography(CBCT) being corrected before irradiation, the accuracy significantly decreased.The most important events were connected with the human factor. Improving human technical level could enhance radiotherapy quality control efficiently.

Static superconducting gantry‑based proton CT combined with X‑ray CT as prior image for FLASH proton therapy

Proton FLASH therapy with an ultra-high dose rate is in urgent need of more accurate treatment plan system(TPS)to promote the development of proton computed tomography(CT)without intrinsic error compared with the transformation from X-ray CT.This paper presents an imaging mode of proton CT based on static superconducting gantry different from the conventional rotational gantry.The beam energy for proton CT is fixed at 350 MeV,which is boosted by a compact proton linac from 230 MeV,and then delivered by the gantry to scan the patient’s body for proton imaging.This study demonstrates that the static superconducting gantry-based proton CT is effective in clinical applications.In particular,the imaging mode,which combines the relative stopping power(RSP)map from X-ray CT as prior knowledge,can produce much a higher accuracy RSP map for TPSs and positioning and achieve ultra-fast image for real-time image-guided radiotherapy.This paper presents the conceptual design of a boosting linac,static superconducting gantry and proton CT imaging equipment.The feasibility of energy enhancement is verified by simulation,and results from Geant4 simulations and reconstruction algorithms are presented,including the simulation verification of the advantage of the imaging mode.

Hi'CT:a pixel sensor-based device for ion tomography

Carbon ions,commonly referred to as particle therapy,have become increasingly popular in the last decade.Accurately predicting the range of ions in tissues is important for the precise delivery of doses in heavy-ion radiotherapy.Range uncertainty is currently the largest contributor to dose uncertainty in normal tissues,leading to the use of safety margins in treatment planning.One potential method is the direct relative stopping measurement(RSP)with ions.Heavy-ion CT(Hi′CT),a compact segmented full digital tomography detector using monolithic active pixel sensors,was designed and evaluated using a 430 MeV/u high-energy carbon ion pencil beam in Geant4.The precise position of the individual carbon ion track can be recorded and reconstructed using a 30μm×30μm small pixel pitch size.Two types of customized image reconstruction algorithms were developed,and their performances were evaluated using three different modules of CAT-PHAN 600-series phantoms.The RSP measurement accuracy of the tracking algorithm for different types of materials in the CTP404 module was less than 1%.In terms of spatial resolution,the tracking algorithm could achieve a 20%modulation transfer function normalization value of CTP528 imaging results at 5 lp/cm,which is significantly better than that of the fast imaging algorithm(3 lp/cm).The density resolution obtained using the tracking algorithm of the customized CTP515 was approximately 10.5%.In conclusion,a compact digital Hi'CT system was designed,and its nominal performance was evaluated in a simulation.The RSP resolution and image quality provide potential feasibility for scanning most parts of an adult body or pediatric patient,particularly for head and neck tumor treatment.

Multi-objective optimization of inverse planning for accurate radiotherapy

The multi-objective optimization of inverse planning based on the Pareto solution set, according to the multi-objective character of inverse planning in accurate radiotherapy, was studied in this paper. Firstly, the clinical requirements of a treatment plan were transformed into a multi-objective optimization problem with multiple constraints. Then, the fast and elitist multi-objective Non-dominated Sorting Genetic Algorithm （NSGA-） was introduced to optimize the problem. A clinical example was tested using this method. The results show that an obtained set of non-dominated solutions were uniformly distributed and the corresponding dose distribution of each solution not only approached the expected dose distribution, but also met the dosevolume constraints. It was indicated that the clinical requirements were better satisfied using the method and the planner could select the optimal treatment plan from the non-dominated solution set.

Photon Dose Calculation Method Based on Monte Carlo Finite-Size Pencil Beam Model in Accurate Radiotherapy

This study mainly focused on the key technologies,the photon dose calculation based on the Monte Carlo Finite-Size Pencil Beam(MCFSPB)model in the Accurate Radiotherapy System(ARTS).In the MCFSPB model,the acquisition of pencil beam kernel is one of the most important technologies.In this study,by analyzing the demerits of the clinical pencil beam dose calculation methods,a new pencil beam kernel model was developed based on the Monte Carlo(MC)simulation and the technology of medical accelerator energy spectrum reconstruction.which greatly improved the accuracy of calculated result.According to the axial symmetry principle,only part of simulation results was used for the data of pencil beam kernel,which greatly reduced the data quantity of the pencil beam and reduced calculated time.Based on the above studies,the MCFSPB method was designed and implemented by the Visual C++development tool.With several tests including the comparisons among the American Association of Physicists in Medicine(AAPM)No.55 Report sample and the ion chamber measurement of lung-simulating inhomogeneous phantom in clinical treatment plan,the results showed that the maximum error of most calculated point was less than 0.5%in the homogeneous phantom and less than 3%in the heterogeneous phantom.This method met the clinical criteria,and would be expected to be used as a fast and accurate dose engine for clinic TPS.

CT-MRI可兼容定位装置在精准放疗中的应用

为提高精准放疗中靶区和正常组织或器官勾画的准确度及放疗的精准度,减少放疗患者的放射性损伤,提高患者的生存率,充分利用医院现有的MRI诊断设备,使用CT和MRI可兼容固定装置,使放疗患者在模拟定位过程中保持相同体位,将CT和MR定位图像融合后进行勾画。同时,该装置还可减少基层医院因缺乏放疗专用MR模拟定位机带来的不便,提高MRI设备的重复使用率,一定程度上减轻患者的经济负担,节约放疗医师时间,提高勾画效率。

动态调强精准放射治疗计划系统KylinRay-IMRT的研发及验证

Kylin Ray-IMRT是精准放射治疗系统Kylin Ray中放疗计划制定子系统,其目标是为精准放射治疗的实施提供精准放疗计划制定平台。该文对Kylin Ray-IMRT的系统设计、主要功能以及关键技术进行介绍。Kylin Ray-IMRT支持三维适形放疗、调强放疗等多种放疗计划的制定,主要包括病人数据管理模块、影像配准与融合、影像勾画、三维重建、三维适形正向计划设计、逆向调强计划设计、计划评估与比较、报告输出等功能模块。根据中国医药行业标准YY/T 0889—2013《调强放射治疗计划系统性能和试验方法》进行系统测试,结果显示Kylin Ray-IMRT性能完全符合标准要求。

270例脑胶质瘤患者术后精确放疗的临床观察

目的探讨脑胶质瘤术后精确放疗及预后的影响因素。方法收集2005年7月至2014年5月收治的270例脑胶质瘤术后精确放疗患者,单因素和多因素分析年龄、性别、KPS、肿瘤部位、放疗手术时间、病理分级、手术方式及是否术后同步放化疗等对脑胶质瘤患者术后放疗总生存时间(OS)的影响。结果全组患者的1年生存率79%,2年生存率55%,3年生存率46%,OS为30个月。单因素分析显示KPS评分(P=0.012),病理分级(P<0.001)及手术切除程度(P<0.001)影响胶质瘤患者术后OS的因素。Cox风险比例回归分析显示KPS(P=0.002)、病理分级(P<0.001)、手术切除程度(P<0.001)及同步化疗是影响患者的独立预后因素。结论患者一般状况好、病理低级别、手术切除程度高有益于胶质瘤患者术后精确放疗获益。

基于ITK与VTK的配准融合方法的研究与应用

在精确放射治疗计划系统中,使用融合技术,可以充分利用多种医学影像的信息,为临床诊断提供更多、更准确的信息。为了保证融合的质量,在融合之前,必须进行配准。常用配准方法中,自动配准是目前的研究热点,然而精度与速度问题却制约了它在精确放射治疗计划系统中的应用。提出了一种结合ITK与VTK的基于互信息的多分辨率自动配准融合方法。详细描述了算法原理与实现流程,并基于实际病例影像数据进行了测试。测试结果表明,该方法的配准效果良好,在精度和速度上均可满足精确放疗的需求。

精确放射治疗计划系统中快速三维重建方法的研究与应用

在放射治疗计划系统中,为了精确地照射靶区避开危及器官,有必要对勾画的二维轮廓信息进行三维重建。现有的三维重建方法难以在拟合真实度和实时性上同时满足临床需求。通过对等值面提取算法进行改进,本文设计了一种快速三维重建流程,并基于可视化开发包(VTK)加以实现。多套来自真实病人影像数据的测试结果表明,快速三维重建法得到的面模型表面光滑,有效避免了"阶梯"效应;面片和顶点数目大幅度削减;与一般的等值面提取算法比较绘制时间大大减少。在保证真实拟合原始解剖结构的前提下,文中的方法改善了重建效果、提高了绘制速度,不仅可应用在精确三维放射治疗计划系统中,也可扩展应用在其他领域。

精确放疗治疗甲状腺癌的研究进展

甲状腺癌是最常见的内分泌系统恶性肿瘤,按组织病理类型可以分为乳头状甲状腺癌、滤泡状甲状腺癌、髓样甲状腺癌和未分化型甲状腺癌。前两者因分化水平较高统称为分化型甲状腺癌。分化型甲状腺癌首选手术治疗,其次针对术中未能切除的残余病灶进行放射碘治疗。外照射放疗在分化型甲状腺癌及甲状腺髓样癌中的作用仅局限于手术治疗失败、肿瘤不能切除或者有肉眼可见远处转移灶残留的患者。精确放疗可增加肿瘤的局部控制率,减少正常组织的放射损伤。而甲状腺未分化癌大多数不能完全手术切除,外照射放疗联合化疗具有重要作用。放疗作为术前、术后综合治疗的一部分发挥作用,也可以采用单纯放疗的形式缓解症状、控制病变生长,从而延长生存期,起到姑息治疗的目的。

PHILIPS大孔径CT模拟定位机影像质量控制方法研究

目的通过对CT模拟定位机质量控制模体的测试,对CT模拟定位机的各项指标进行质量控制,分析影响图像质量的因素,保证图像质量。方法利用PHILIPS大孔径CT模拟定位机分别对Catphan504模体四大部分进行头部标准质量控制方案轴向扫描,测试其层厚、CT值线性、均匀性、噪声、空间分辨率、密度分辨率。层厚测试扫描条件为120 kV,280 mAs,层厚9.0、6.0、3.0、1.5 mm,旋转时间0.75 s,算法采用EB;CT值线性扫描条件为120 kV,280 mAs,层厚9.0 mm,旋转时间0.75 s,算法EB、B;均匀性、噪声、空间分辨率扫描条件均为120 kV,280 mAs,层厚9.0 mm,旋转时间0.75 s,算法EB;密度分辨率扫描条件为120 kV,220 mAs、240 mAs、260 mAs、280 mAs,层厚9.0 mm,旋转时间0.75 s,算法EB。结果 9.0 mm、6.0 mm、3.0 mm、1.5 mm标称层厚的测试结果分别为8.82 mm、5.80 mm、2.95 mm、1.55 mm;对于CT值线性,EB、B两种算法的对比度标度分别为1.79×10^(-4) cmHu^(-1)、1.93×10^(-4) cmHu^(-1);均匀性为3.9 Hu;噪声水平为0.34%;空间分辨率为6 LP/cm;220 mAs、240 mAs、260 mAs、280 mAs条件下,密度分辨率分别为4 mm@1%、3 mm@1%、2 mm@1%、2 mm@1%。CT值线性在EB算法条件下,对比度标度近似等于参考值下限值,密度分辨率在220 mAs、240 mAs条件下,其测量值低于参考值,其他测试项目结果均符合要求。结论通过对各项目的检测可保证影像质量最优化,进而保证精确放射治疗的实施。